N-acetylcysteine to reduce kidney and liver injury associated with drug-resistant tuberculosis treatment

Abstract Background New drug classes and regimens have shortened the treatment duration for drug-resistant tuberculosis, but adverse events (AEs) and organ toxicity remain unacceptably common. N-acetylcysteine (NAC) has demonstrated potential in reducing kidney and liver toxicity in other clinical settings, but efficacy in drug-resistant tuberculosis treatment has not been rigorously evaluated. Method A randomized controlled trial (PACTR202007736854169) was conducted at Kibong’oto Infectious Disease Hospital in Tanzania to assess the efficacy of NAC in reducing AEs in patients undergoing rifampin-resistant pulmonary tuberculosis treatment. Participants received an all-oral standardized rifampin-resistant regimen alone, with NAC 900 mg daily, or NAC 900 mg twice daily for 6 months. AEs, severe AEs, and renal and liver toxicity were monitored monthly and classified according to the Risk, Injury, Failure, Loss, and End-stage kidney disease criteria and National Cancer Institute Common Terminology Criteria for Adverse Events. Incident ratios and Kaplan-Meier curves were employed to compare group event occurrences. Results 66 patients (mean age 47±12 years; 80% male) were randomized into three groups of 22. One hundred and fifty-eight AEs were recorded: 52 (33%) in the standard treatment group, 55 (35%) in the NAC 900 mg daily group, and 51 (32%) in the NAC 900 mg twice daily group (p>0.99). Severe AEs were observed in 4 patients in the standard group, 2 in the NAC 900 mg daily group, and 3 in the NAC 900 mg twice daily group. Renal toxicity was more prevalent in the standard treatment group (45% vs. 23%; p=0.058), with a shorter onset of time to toxicity ( χ 2 = 3.199; p=0.074). Liver injury events were rare across all groups. Conclusion Among Tanzanian adults receiving rifampin-resistant tuberculosis treatment, NAC did not significantly reduce overall AEs but demonstrated important trends in reducing renal toxicity.